Abstract
The synthesis of virulence factors and other exoproteins inStaphylococcus aureus is controlled by the global regulator,agr. Expression of secreted proteins is up-regulated in the postexponential growth phase, whereas expression of surface proteins is down-regulated byagr. Theagr locus consists of two divergent operons, transcribed from neighboring but non-overlapping promoters, P2 and P3. The P2 operon sequence, reported here, contains 4 open reading frames,agr A, C, D, andB, of whichA andC appear to encode proteins of a classical 2-component signal transduction pathway. The P3 operon specifies a 0.5 kb transcript, RNA III, which is the actual effector of theagr response, and, incidentally, encodes theagr-regulated peptide δ-hemolysin. Transcriptional fusions have shown that both P2 and P3 areagr sensitive (function in anagr + but not in anagr background) and deletion analysis has shown that all four of the P2 ORFs are involved;agrA andagrC seem to be absolutely required for the transcriptional activation of theagr locus, whereasagrB andagrD seem to be partially required. Since transcription of P2 requires P2 operon products, the P2 operon is autocatalytic, and is thus admirably suited to the need for rapid production of exo-proteins at a time when overall growth is coming to a halt.
Similar content being viewed by others
References
Abdelnour A, Arvidson S, Bremell T, Ruden C, Tarkowski A (1993) The accessory gene regulator (agr) controlsStaphylococcus aureus virulence in a murine arthritis model. Infect Immun 61:3879–3885
Arvidson S, Janzon L, Lofdahl S (1990) The role of the delta-lysin gene (hld) in theagr-dependent regulation of exoprotein synthesis inStaphylococcus aureus. In: Novick RP (ed) Molecular biology of the Staphylococci. VCH Publishers, New York, pp 421–432
Arvidson S, Janzon L, Lofdahl S, Morfeldt E (1989) The exoprotein regulatory regionexp ofS. aureus. In: Butler EO, Moseley EB (eds) Genetic transformation and expression. Intercept, Wimbourne, Dorset UK, Ltd 511–518
Arvidson SO (1983) Extracellular enzymes fromStaphylococcus aureus. In: Easmon CF, Adlam C (eds) Staphylococci and staphyloccocal infections. vol 2. Academic Press, London, pp 745–808
Balaban N, Novick RP (1995) Autocrine regulation of toxin synthesis byStaphylococcus aureus. Proc Natl Acad Sci USA 92:1619–1623
Bernheimer AW Schwartz LL (1963) Isolation and composition of staphylococcal alpha toxin. J Gen Microbiol 30:455–468
Bjorklind A, Arvidson S (1980) Mutants ofStaphylococcus aureus affected in the regulation of exoprotein synthesis. FEMS Microbiol Lett 7: 203–206
Connell N, Han Z, Moreno F, Kolter R (1987) AnE. coli promoter induced by the cessation of growth. Mol Microbiol 1:195–201
Engelman DM, Steitz TA, Goldman A (1986) Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Ann Rev Biophys Chem 15:321–353
Foster TJ, O'Reilly M, Phonimdaeng P, Cooney J, Patel AH, Bramley AJ (1990) Genetic studies of virulence factors ofStaphylococcus aureus. Properties of coagulase and gamma-toxin, alpha-toxin, beta-toxin and protein A in the pathogenesis ofS. aureus infections. In: Novick RP (ed) Molecular biology of the Staphylococci. VCH Publishers, New York, pp 403–420
Gennaro ML, Novick RP (1988) An enhancer of DNA replication. J Bacteriol 170:5709–5717
Gray GS, Kehoe M (1984) Primary sequence of the alpha-toxin gene fromStaphylococcus aureus wood 46. Infect Immun 46:615–618
Horinouchi S, Weisblum B (1982) Nucleotide sequence and functional map of pC194, a plasmid that specifies inducible chloramphenicol resistance. J Bacteriol 150: 815–825
Janzon L, Arvidson S (1990) The role of the delta-lysin gene (hld) in the regulation of virulence genes by the accessory gene regulator (agr) inStaphylococcus aureus. EMBO J 9:1391–1399
Janzon L, Lofdahl S, Arvidson S (1989) Identification and nucleotide sequence of the delta-lysin gene,hld, adjacent to the accessory gene regulator (agr) ofStaphylococcus aureus. Mol Gen Genet 219:480–485
Kornblum J, Kreiswirth B, Projan S, Ross H, Novick RP (1990)Agr: a polycistronic locus regulating exoprotein synthesis inStaphylococcus aureus. Molecular biology of the Staphylococci. VCH Publishers, New York, NY, 373–402
Kreiswirth B, Lofdahl S, Bettey M, O'Reilly M, Schlievert P, Bergdoll M, Novick RP (1983) The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 305:709–712
Losick R, Youngman P, Piggot PJ (1986) Genetics of endospore formation inBacillus subtilis. Annu Rev Genet 20:625–669
Magasanik B (1982) Genetic control of nitrogen assimilation in bacteria. Annu Rev Genet 16:135–168
Mallonee DH, Glatz BA, Pattee P (1982) Chromosomal mapping of a gene affecting enterotoxin A production inStaphylococcus aureus. Appl Environ Microbiol 43:397–402
McLaughlin JR, Murray CL, Rabinowitz JC (1981) Unique features in the ribosome binding site sequence of the gram-positiveStaphylococcus aureus β-lactamase gene. J Biol Chem 256:11283–11291
Morfeldt E, Janzon L, Arvidson S, Lofdahl S (1988) Cloning of a chromosomal locus (exp) which regulates the expression of several exoprotein genes inStaphylococcus aureus. Mol Gen Genet 211:435–440
Nixon BT, Ronson CW, Ausubel FM (1986) Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with the nitrogen assimilation regulatory genesntrB andntrC. Proc Natl Acad Sci USA 83:7850–7854
Novick R (1967) Properties of a cryptic high-frequency transducing phase inStaphylococcus aureus. Virology 33:155–166
Novick R, Kornblum J, Kreiswirth B, Projan S, Ross H (1989)Agr: a complex locus regulating post-exponential phase exoprotein synthesis inStaphylococcus aureus. In: Butler LO, Moseley, BEB (eds) Genetic transformation and expression. Intercept, Andover, Hants, UK, pp 495–510
Novick RP, Brodsky RJ (1972) Studies on plasmid replication: plasmid incompatibility and establishment inStaphylococcus aureus. J Mol Biol 68:285–302
Novick RP, Kornblum J (1990) Regulation of post-exponential phase exoprotein synthesis inStaphylococcus aureus. In: Ayoub EM (ed) Microbial determinants of virulence and host response. American Society for Microbiology, Washington, DC, pp 3–18
Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S (1993) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12:3967–3975
O'Callaghan CH, Morris A, Kirby SM, Shingler AH (1972) Novel method for detection of β-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Ag Chemother 1: 283–288
Peng HL, Novick RP, Kreiswirth B, Kornblum J, Schlievert P (1988) Cloning, characterization and sequencing of an accessory gene regulator (agr) inStaphylococcus aureus. J Bacteriol 179:4365–4372
Projan SJ, Carleton S, Novick RP (1983) Determination of plasmid copy number by fluorescence densitometry. Plasmid 9:182–190
Ranellin DM, Jones CL, Johns MB, Mussey GJ, Khan SA (1985) Molecular cloning of staphylococcal enterotoxin B gene inEscherichia coli andStaphylococcus aureus. Proc Natl Acad Sci USA 82:5850–5854
Recsei P, Kreiswirth B, O'Reilly M, Schlievert P, Gruss A, Novick RP (1986) Regulation of exoprotein gene expression byagr. Mol Gen Genet 202:58–61
Ross H (1989) Molecular genetics of exoprotein regulation inStaphylococcus aureus. Doctoral dissertation. New York University
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual (2nd edn) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
Sanger F, Coulson A, Barrell BG, Smith AJH, Roe BA (1980) Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol 143:161–178
Scarlato V, Arico B, Pragnola A, Rappuoli R (1989) Sequential activation and environmental regulation of virulence genes inBordetella pertussis. EMBO J 10: 3971–3975
Stock JB, Ninfa AJ, Stock AM (1989) Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiol Rev 53:450–490
Vandenesch F, Projan S, Kreiswirth B, Etienne J, Novick RP (1993)Agr-related sequences inStaphylococcus lugdunensis. FEMS Microbiol Lett 111: 115–122
Wang PZ, Projan SJ, Leason K, Novick RP (1987) Translational fusion with a secretory enzyme as an indicator. J Bacteriol 169:3082–3087
Wyman L, Novick RP (1974) Studies on plasmid replication. IV. Complementation of replication-defective mutants by an incompatibility-deficient plasmid. Molec Gen Genet 135:149–161
Author information
Authors and Affiliations
Additional information
Communicated by W. Goebel
Rights and permissions
About this article
Cite this article
Novick, R.P., Projan, S.J., Kornblum, J. et al. Theagr P2 operon: An autocatalytic sensory transduction system inStaphylococcus aureus . Molec. Gen. Genet. 248, 446–458 (1995). https://doi.org/10.1007/BF02191645
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02191645